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Mangoni M, Sottili M, Gerini C, et al. A PPAR-gamma agonist protects from radiation-induced intestinal toxicity. United European Gastroenterol J. 2016;5(2):218-226doi: 10.1177/2050640616640443.
Mangoni, M., Sottili, M., Gerini, C., Desideri, I., Bastida, C., Pallotta, S., Castiglione, F., Bonomo, P., Meattini, I., Greto, D., Cappelli, S., Di Brina, L., Loi, M., Biti, G., & Livi, L. (2017). A PPAR-gamma agonist protects from radiation-induced intestinal toxicity. United European gastroenterology journal, 5(2), 218-226. https://doi.org/10.1177/2050640616640443
Mangoni, Monica, et al. "A PPAR-gamma agonist protects from radiation-induced intestinal toxicity." United European gastroenterology journal vol. 5,2 (2017): 218-226. doi: https://doi.org/10.1177/2050640616640443
Mangoni M, Sottili M, Gerini C, Desideri I, Bastida C, Pallotta S, Castiglione F, Bonomo P, Meattini I, Greto D, Cappelli S, Di Brina L, Loi M, Biti G, Livi L. A PPAR-gamma agonist protects from radiation-induced intestinal toxicity. United European Gastroenterol J. 2017 Mar;5(2):218-226. doi: 10.1177/2050640616640443. Epub 2016 Jul 08. PMID: 28344789; PMCID: PMC5349355.
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United European Gastroenterol J. 2017 Mar;5(2):218-226. doi: 10.1177/2050640616640443. Epub 2016 Jul 08.

A PPAR-gamma agonist protects from radiation-induced intestinal toxicity.

United European gastroenterology journal

Monica Mangoni, Mariangela Sottili, Chiara Gerini, Isacco Desideri, Cinzia Bastida, Stefania Pallotta, Francesca Castiglione, Pierluigi Bonomo, Icro Meattini, Daniela Greto, Sabrina Cappelli, Lucia Di Brina, Mauro Loi, Giampaolo Biti, Lorenzo Livi

Affiliations

  1. Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Firenze, Italy.
  2. Medical Physic Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Firenze, Italy.
  3. Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy.

PMID: 28344789 PMCID: PMC5349355 DOI: 10.1177/2050640616640443

Abstract

OBJECTIVE: Because of its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-neoplastic properties, the PPAR-γ agonist rosiglitazone is an interesting drug for investigating for use in the prevention and treatment of radiation-induced intestinal damage. We aimed to evaluate the radioprotective effect of rosiglitazone in a murine model of acute intestinal damage, assessing whether radioprotection is selective for normal tissues or also occurs in tumour cells.

METHODS: Mice were total-body irradiated (12 Gy), with or without rosiglitazone (5 mg/kg/day). After 24 and 72 hours, mice were sacrificed and the jejunum was collected. HT-29 human colon cancer cells were irradiated with a single dose of 2 (1000 cells), 4 (1500 cells) or 6 (2000 cells) Gy, with or without adding rosiglitazone (20 µM) 1 hour before irradiation. HT-29-xenografted CD1 mice were irradiated (16 Gy) with or without rosiglitazone; tumour volumes were measured for 33 days.

RESULTS: Rosiglitazone markedly reduced histological signs of altered bowel structures, that is, villi shortening, submucosal thickening, necrotic changes in crypts, oedema, apoptosis, and inflammatory infiltrate induced by irradiation. Rosiglitazone significantly decreased p-NF-kB p65 phosphorylation and TGFβ protein expression at 24 and 72 hours post-irradiation and significantly decreased gene expression of

CONCLUSION: Rosiglitazone exerts a protective effect on normal tissues and reduces alterations in bowel structures and inflammation in a radiation-induced bowel toxicity model, without interfering with the radiation effect on HT-29 cancer cells. PPAR-γ agonists should be further investigated for their application in abdominal and pelvic irradiation.

Keywords: PPAR-gamma agonists; Rosiglitazone; bowel; radiation-induced toxicity; radioprotection

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